This application relates to the field of antimicrobial compounds.
Gram-positive and Gram-negative pathogens pose a serious threat to public health. Two Gram-positive pathogens, Staphylococcus aureus and Enterococcus fecalis/fecium, are primarily nosocomial (hospital-acquired) pathogens; together, they presently account for the majority of nosocomial diseases. A third organism, Streptococcus pneumoniae, is generally a community-acquired pathogen. Gram-negative bacteria such as Escherichia coli, Salmonella typhimurium, and Pseudomonas aeruginosa, also cause significant diseases in humans.
Staphylococcus aureus is the most frequent cause of nosocomial bacteremia and skin/wound infection and the second most frequent cause of nosocomial lower respiratory infection. Enterococcus fecalis/fecium ranks third behind Staphylococcus aureus and Escherichia coli as a cause of nosocomial septicemia, endocarditis, and infections of wounds and the urinary tract. Streptococcus pneumoniae causes several serious and potentially life-threatening diseases. In the United States it is estimated that Streptococcus pneumoniae accounts annually for 6,000 cases of pneumococcal meningitis, a half million cases of pneumonia, 55,000 cases of bacteremia, and 6 million cases of otitis media. Annual mortality from Streptococcus pneumoniae-induced disease is estimated to be 40,000 in the United States and 3-5 million globally.
There is a rapidly growing global crisis in the clinical management of life-threatening infectious disease caused by multi-antibiotic-resistant strains of the Gram-positive pathogens Streptococcus, Enterococcus, and Staphylococcus, the Gram-negative pathogens Escherichia, Salmonella, and Pseudomonas, and certain mycoplasmata. To meet this crisis successfully, there is thus a need for new antibiotic compounds which can selectively attack novel targets in these organisms.